Acute otitis media (AOM) is one of the most common infectious diseases of children and the most common infection for which antibiotics are prescribed in the United States (Daly, et al. (1999) Pediatrics 103:1158-1166; McCaig, et al. (2002) JAMA 287:3096-3102). Streptococcus pneumoniae remains one of the most prevalent causes of AOM even after the advent of the heptavalent conjugate vaccine (Coker, et al. (2010) JAMA 304:2161-2169). Vaccination is viewed as a critical method of prevention but has been largely unsuccessful in changing the incidence of AOM. The 23-valent polysaccharide vaccine does not elicit antibodies in children under age 2 and is not protective against AOM in any age group. The heptavalent conjugate pneumococcal vaccine (PREVNAR) is highly protective against invasive disease from birth but again fails to significantly impact the rate of AOM (Eskola, et al. (2001) N. Engl. J. Med. 344:403-409). The high effect of AOM on children's medical care and the absence of effective preventive intervention indicates that new vaccine concepts are urgently needed.
Otitis media caused by S. pneumoniae is a significant medical burden in children. Although the advent of the pneumococcal polyvalent conjugate vaccine PREVNAR (PCV7) has decreased the overall burden of pneumococcal disease, the suboptimal mucosal immune response elicited by this vaccine does not provide effective protection. Even with vaccination, AOM is the leading cause of pediatric physician visits and is responsible for a majority of the antibiotics prescribed to young children (Daly, et al. (1999) supra; McCaig, et al. (2002) supra). Furthermore, as is the risk with all polysaccharide capsule-based vaccines, the risk of an increasing burden of non-vaccine serotypes remains problematic and quickly emerges (Block, et al. (2004) Pediatr. Infect. Dis. J. 23:829-833; Eskola, et al. (2001) supra). This underscores the importance of development of new vaccination strategies that would confer cross-serotype protection as well as a greater understanding of host mucosal immunity.
Studies in animal models have demonstrated that the intranasal route of vaccination is particularly effective at inducing immune responses in the nasal passage and middle ear for protection against AOM (Sabirov & Metzger (2006) Vaccine 24:5584-5592). Further, application of live, attenuated S. pneumoniae mediates a potent, serotype-independent mucosal and humoral immune response that was protective against subsequent invasive challenge (Roche, et al. (2007) Infect. Immun. 75:2469-2475). These studies suggest that a vaccine effective against AOM should optimally be live, attenuated, and be given intranasally. However, these vaccines may not be optimal because they were generated by deleting several important, highly immunogenic virulence factors, which are currently being developed as components of protein-based vaccines against S. pneumoniae. Therefore, there is a need in the art for alternative vaccines for the prevention of pneumococcal disease.